Despite all the advances in atherosclerosis over the last several decades, surprisingly we lack direct evidence of the critical factors controlling the final events that convert an atherosclerotic lesion from a collection of fatty foam cells to an occlusive, ruptured, procoagulant, and life threatening lesion. The bulk of the evidence supports the hypothesis that these final events occur as a result of inflammatory changes in the lesion. This program projects attempts to test that hypothesis by combining newly developed approaches that allow us to directly visualize the plaque non-invasively in humans with experimental models in the mouse. The human studies will utilize state of the art genomics, including single nucleotide polymorphisms and expression arrays to determine the correlation of specific inflammatory genes with plaque progression. The animal studies will utilize a mouse model of plaque rupture to examine the role of the same genes as manifest in the plaque macrophage and the endothelial cell in these final critical events.